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Primary hyperparathyroidism influences the expression of inflammatory and metabolic genes in adipose tissue.

Christensen MH, Dankel SN, Nordbø Y, Varhaug JE, Almås B, Lien EA, Mellgren G - PLoS ONE (2011)

Bottom Line: We found 608 differentially expressed genes (q-value<0.05), of which 347 were up-regulated and 261 were down-regulated.Analysis of transcription factor binding sites present in the differentially expressed genes corroborated the up-regulation of inflammatory processes.Our findings demonstrate that PHPT strongly influences gene regulation in fat tissue, which may result in altered adipose tissue function and release of pathogenic factors that increase the risk of CVD.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medicine, University of Bergen, Bergen, Norway.

ABSTRACT

Background: Primary hyperparathyroidism (PHPT) is characterised by increased production of parathyroid hormone (PTH) resulting in elevated serum calcium levels. The influence on bone metabolism with altered bone resorption is the most studied clinical condition in PHPT. In addition to this, patients with PHPT are at increased risk of non-skeletal diseases, such as impaired insulin sensitivity, arterial hypertension and increased risk of death by cardiovascular diseases (CVD), possibly mediated by a chronic low-grade inflammation. The aim of this study was to investigate whether adipose tissue reflects the low-grade inflammation observed in PHPT patients.

Methodology/principal findings: Subcutaneous fat tissue from the neck was sampled from 16 non-obese patients with PHPT and from 16 patients operated for benign thyroid diseases, serving as weight-matched controls. RNA was extracted and global gene expression was analysed with Illumina BeadArray Technology. We found 608 differentially expressed genes (q-value<0.05), of which 347 were up-regulated and 261 were down-regulated. Gene ontology analysis showed that PHPT patients expressed increased levels of genes involved in immunity and defense (e.g. matrix metallopeptidase 9, S100 calcium binding protein A8 and A9, CD14, folate receptor 2), and reduced levels of genes involved in metabolic processes. Analysis of transcription factor binding sites present in the differentially expressed genes corroborated the up-regulation of inflammatory processes.

Conclusions/significance: Our findings demonstrate that PHPT strongly influences gene regulation in fat tissue, which may result in altered adipose tissue function and release of pathogenic factors that increase the risk of CVD.

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Related in: MedlinePlus

Correspondence analysis showing projection of samples.Patients with primary hyperparathyroidism are shown with red dots and the control group are shown with blue squares. The first principal component shows the largest variance in the dataset with 8.83% and the second principal component represents the second largest variance with 6.69%. Patients with primary hyperparathyroidism are separated from the control group along both axes.
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pone-0020481-g001: Correspondence analysis showing projection of samples.Patients with primary hyperparathyroidism are shown with red dots and the control group are shown with blue squares. The first principal component shows the largest variance in the dataset with 8.83% and the second principal component represents the second largest variance with 6.69%. Patients with primary hyperparathyroidism are separated from the control group along both axes.

Mentions: Microarray analysis revealed a difference in the adipose tissue gene expression in patients with PHPT compared to controls. Correspondence analysis showed that the two groups were separated by distinct gene expression patterns, where the first principal component represented 8.83% of the total variance and the second principal component 6.69% (Fig. 1). Using Significance Analysis of Microarray (SAM), we found 608 differentially expressed genes with q-value<0.05, thereof 347 up-regulated and 261 down-regulated genes in PHPT patients compared to the control group. Several of the most up-regulated genes have previously been implicated in inflammatory diseases whereas many of the down-regulated genes play roles in lipid and carbohydrate metabolism (Table 3). Analysing the data including only females aged 27–65 years we found 162 differentially expressed genes with q-value<0.05. Of these, 113 genes were up-regulated and 49 genes were down-regulated. Correspondence Analysis of this age-matched subgroup showed equally marked differences in gene expression, with first and second principle component variance of 11.38% and 9.851%, respectively.


Primary hyperparathyroidism influences the expression of inflammatory and metabolic genes in adipose tissue.

Christensen MH, Dankel SN, Nordbø Y, Varhaug JE, Almås B, Lien EA, Mellgren G - PLoS ONE (2011)

Correspondence analysis showing projection of samples.Patients with primary hyperparathyroidism are shown with red dots and the control group are shown with blue squares. The first principal component shows the largest variance in the dataset with 8.83% and the second principal component represents the second largest variance with 6.69%. Patients with primary hyperparathyroidism are separated from the control group along both axes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3117792&req=5

pone-0020481-g001: Correspondence analysis showing projection of samples.Patients with primary hyperparathyroidism are shown with red dots and the control group are shown with blue squares. The first principal component shows the largest variance in the dataset with 8.83% and the second principal component represents the second largest variance with 6.69%. Patients with primary hyperparathyroidism are separated from the control group along both axes.
Mentions: Microarray analysis revealed a difference in the adipose tissue gene expression in patients with PHPT compared to controls. Correspondence analysis showed that the two groups were separated by distinct gene expression patterns, where the first principal component represented 8.83% of the total variance and the second principal component 6.69% (Fig. 1). Using Significance Analysis of Microarray (SAM), we found 608 differentially expressed genes with q-value<0.05, thereof 347 up-regulated and 261 down-regulated genes in PHPT patients compared to the control group. Several of the most up-regulated genes have previously been implicated in inflammatory diseases whereas many of the down-regulated genes play roles in lipid and carbohydrate metabolism (Table 3). Analysing the data including only females aged 27–65 years we found 162 differentially expressed genes with q-value<0.05. Of these, 113 genes were up-regulated and 49 genes were down-regulated. Correspondence Analysis of this age-matched subgroup showed equally marked differences in gene expression, with first and second principle component variance of 11.38% and 9.851%, respectively.

Bottom Line: We found 608 differentially expressed genes (q-value<0.05), of which 347 were up-regulated and 261 were down-regulated.Analysis of transcription factor binding sites present in the differentially expressed genes corroborated the up-regulation of inflammatory processes.Our findings demonstrate that PHPT strongly influences gene regulation in fat tissue, which may result in altered adipose tissue function and release of pathogenic factors that increase the risk of CVD.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medicine, University of Bergen, Bergen, Norway.

ABSTRACT

Background: Primary hyperparathyroidism (PHPT) is characterised by increased production of parathyroid hormone (PTH) resulting in elevated serum calcium levels. The influence on bone metabolism with altered bone resorption is the most studied clinical condition in PHPT. In addition to this, patients with PHPT are at increased risk of non-skeletal diseases, such as impaired insulin sensitivity, arterial hypertension and increased risk of death by cardiovascular diseases (CVD), possibly mediated by a chronic low-grade inflammation. The aim of this study was to investigate whether adipose tissue reflects the low-grade inflammation observed in PHPT patients.

Methodology/principal findings: Subcutaneous fat tissue from the neck was sampled from 16 non-obese patients with PHPT and from 16 patients operated for benign thyroid diseases, serving as weight-matched controls. RNA was extracted and global gene expression was analysed with Illumina BeadArray Technology. We found 608 differentially expressed genes (q-value<0.05), of which 347 were up-regulated and 261 were down-regulated. Gene ontology analysis showed that PHPT patients expressed increased levels of genes involved in immunity and defense (e.g. matrix metallopeptidase 9, S100 calcium binding protein A8 and A9, CD14, folate receptor 2), and reduced levels of genes involved in metabolic processes. Analysis of transcription factor binding sites present in the differentially expressed genes corroborated the up-regulation of inflammatory processes.

Conclusions/significance: Our findings demonstrate that PHPT strongly influences gene regulation in fat tissue, which may result in altered adipose tissue function and release of pathogenic factors that increase the risk of CVD.

Show MeSH
Related in: MedlinePlus